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- Accepted manuscript posted online 3 June 2015, doi: 10.1128/JVI.01162-15 JVI.01162-15
Influenza A virus co-infection through transmission can support high levels of reassortment
- Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322.
ABSTRACT
The reassortment of gene segments between influenza viruses increases genomic diversity and plays an important role in viral evolution. We have shown previously that this process is highly efficient within a co-infected cell and, given synchronous co-infection at moderate or high doses, can give rise to ∼60-70% of progeny shed from an animal host. Conversely, reassortment in vivo can be rendered undetectable by lowering viral doses or extending the time between infections. One might also predict that seeding of transmitted viruses into different sites within the target tissue could limit subsequent reassortment. Given the potential for stochastic factors to restrict reassortment during natural infection, we sought to determine its efficiency in a host co-infected through transmission. Two scenarios were tested in a guinea pig model, using influenza A/Panama/2007/99 (H3N2) virus (wt) and a silently mutated variant (var) thereof as parental virus strains. In the first, co-infection was achieved by exposing a na?ve guinea pig to two cagemates, one infected with wt and the other with var virus. When such exposure led to co-infection, robust reassortment was typically seen, with 50-100% of isolates carrying reassortant genomes at one or more time points. In the second scenario, na?ve guinea pigs were exposed to a cagemate that had been co-inoculated with wt and var viruses. Here, reassortment occurred in the co-inoculated donor host, multiple variants were transmitted, and reassortants were prevalent in the recipient host. Together, these results demonstrate the immense potential for reassortment to generate viral diversity in nature.
Importance Influenza viruses evolve rapidly under selection due to the generation of viral diversity through two mechanisms. The first is the introduction of random errors into the genome by the viral polymerase, which occurs with a frequency of approximately 10-5 errors/nucleotide replicated. The second is reassortment, or the exchange of gene segments between viruses. Reassortment is known to occur readily under well-controlled laboratory conditions, but its frequency in nature is not clear. Here we tested the hypothesis that reassortment efficiency following co-infection through transmission would be reduced compared to that seen with co-inoculation. Contrary to this hypothesis, our results indicate that co-infection achieved through transmission supports high levels of reassortment. These results suggest that reassortment is not exquisitely sensitive to stochastic effects associated with transmission and likely occurs in nature whenever a host is infected productively with more than one influenza A virus.
